Tau is a phosphoprotein having a physiological function of binding to tubulin to stabilise microtubules. The degree of tau phosphorylation determines the binding affinity to microtubules-tau hyperphosphorylation leads to weaker microtubule binding. There is growing evidence that tau malfunction is implicated in, or triggers neurodegeneration and dementia. There is therefore significant interest in the molecular imaging of tau in vivo.
EP 1574500 A1 (BF Research Institute Inc.) discloses diagnostic probes for Tau proteins which comprise optionally radiolabelled compounds of structure:

wherein:                R1, R2, and R3 independently are H, Hal, OH, COOH, SO3H, NH2, NO2, CO—NH—NH2, C1-4 alkyl or O—C1-4 alkyl, wherein two R1 groups together, may form a benzene ring;        R4 and R5 are independently H or C1-4 alkyl; and        m and n are independently integers of value 0 to 4.        
WO 2012/067863 discloses that quinolines can be radiolabelled with radioisotopes suitable for PET or SPECT imaging to provide Tau imaging agents. WO 2012/067863 mentions that automated methods optionally including cassettes can be used, but does not describe particular precursors, methods or cassettes.
WO 2012/057312 A1 discloses Tau imaging radiotracers which are radiolabelled compounds of Formula (I):
wherein
A is
R1 is Hal, a —C(═O)-lower alkyl group (said alkyl group may be each independently substituted with one or more substituents selected from the group consisting of NRaRb, Hal, and OH), a lower alkyl group (said alkyl group may be each independently substituted with one or more substituents selected from the group consisting of Hal and OH), an —O-lower alkyl group (said alkyl group may be each independently substituted with one or more substituents selected from the group consisting of Hal and OH), or
wherein
R4 and R5 are each independently H, a lower alkyl group, or a cycloalkyl group, or R4, R5, and the nitrogen atom to which they are attached are together form a 3- to 8-membered nitrogen-containing aliphatic ring (one or more carbon atoms constituting said nitrogen-containing aliphatic ring may be replaced by a N, S or O atom, and when the carbon atom is replaced by a N atom, said N atom may be substituted with a lower alkyl group), or
R4 and the nitrogen atom to which it is attached, together with the ring A, form an 8- to 16-membered nitrogen-containing fused bicyclic ring system (one or more carbon atoms constituting said nitrogen-containing fused bicyclic ring system may be replaced by a N, S or O atom, and when the carbon atom is replaced by a nitrogen atom, said nitrogen atom may be substituted with a lower alkyl group), and R5 is H, a lower alkyl group, or a cycloalkyl group,
where a solid line intersected with a broken line designates a linkage with another structural portion in the general formulae above,
R2 or R3 is each independently Hal, OH, COOH, SO3H, NO2, SH, NRaRb, a lower alkyl group (said alkyl group may be each independently substituted with one or more substituents selected from the group consisting of Hal and OH), or an —O-lower alkyl group (said alkyl group may be each independently substituted with one or more substituents selected from the group consisting of Hal and OH),
the ring A is unsubstituted or substituted with R6 (wherein R6 is one or more substituents independently selected from the group consisting of Hal, OH, COOH, SO3H, NO2, SH, NRaRb, a lower alkyl group (said alkyl group may be each independently substituted with one or more substituents selected from the group consisting of Hal and OH), and an —O-lower alkyl group (said alkyl group may be each independently substituted with one or more substituents selected from the group consisting of Hal, OH, and an —O-lower alkyl group-O-lower alkyl group (said alkyl group may be each independently substituted with Hal))),
Ra and Rb are independently H or a lower alkyl group (said alkyl group may be each independently substituted with one or more substituents selected from the group consisting of Hal and OH),
m is an integer from 0 to 4, and
n is an integer from 0 to 4.
WO 2012/057312 A1 teaches that the 18F-radiotracers are purified using a combination of Sep-Pak cartridges followed by semi-preparative HPLC.
Okamura et al [J. Nucl. Med., 54(8), 1420-1427 (2013)] disclose that 18F-arylquinolines, in particular 18F-THK-5105 and 18F-THK-5117 are novel imaging agents for imaging tau pathology in Alzheimer's disease. Okamura et al use the following precursors and radiofluorination method:
Okamura et al use a manual radiolabelling reaction, plus semi-preparative HPLC for purification of the radiotracer.
Blom et al [J. Radioanal. Nucl. Chem., 299, 265-270 (2014)] teach that the radiotracer

[18F]-FMISO, which also incorporates a fluorohydroxypropyl group, can be prepared via an automated radiosynthesis. Blom et al studied various solid-phase extraction (SPE) columns together with the chemical and radiochemical impurities, and concluded that a hydrophilic-lipophilic balanced (HLB), polymer-based cartridge was superior to both a mixed mode (MCX) cartridge and a Sep-Pak C18 cartridge.
There is therefore still a need for alternative and/or improved methods of preparing and purifying the tau imaging agents of WO 2012/057312 A1 and Okamura et al.